Mohammad Arif Hossain1, Katsumi Higaki2, Michiko Shinpo1, Eiji Nanba2, Yoshiyuki Suzuki3, Keiichi Ozono1, Norio Sakai4. 1. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 2. Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago, Japan. 3. Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 4. Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: norio@ped.med.osaka-u.ac.jp.
Abstract
INTRODUCTION: Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 β-galactosidase (β-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. Three subtypes are recognized: early infantile, late infantile, and juvenile/adult. There is no specific therapy for patients with galactosialidosis at this time. OBJECTIVES: The aim of this study was to determine the chaperone effect of N-octyl-4-epi-β-valienamine (NOEV) on β-gal proteins in skin fibroblasts of PPCA-deficit patients. METHODS: β-Gal and neuraminidase activities were measured for the diagnosis of the patients with galactosialidosis. Western blotting for PPCA protein and direct sequencing for CTSA gene were performed. Cultured skin fibroblast were treated with NOEV. RESULTS: We report four novel patients with galactosialidosis: one had the early infantile form and the other three had the juvenile/adult form. We found that NOEV stabilized β-gal activity in lysate from cultured skin fibroblasts from these patients. Treatment with NOEV significantly enhanced β-gal activity in cultured skin fibroblasts in the absence of PPCA. CONCLUSIONS: Our results indicate the possibility that NOEV chaperone therapy might have a beneficial effect, at least in part, for patients with galactosialidosis.
INTRODUCTION:Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 β-galactosidase (β-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. Three subtypes are recognized: early infantile, late infantile, and juvenile/adult. There is no specific therapy for patients with galactosialidosis at this time. OBJECTIVES: The aim of this study was to determine the chaperone effect of N-octyl-4-epi-β-valienamine (NOEV) on β-gal proteins in skin fibroblasts of PPCA-deficitpatients. METHODS: β-Gal and neuraminidase activities were measured for the diagnosis of the patients with galactosialidosis. Western blotting for PPCA protein and direct sequencing for CTSA gene were performed. Cultured skin fibroblast were treated with NOEV. RESULTS: We report four novel patients with galactosialidosis: one had the early infantile form and the other three had the juvenile/adult form. We found that NOEV stabilized β-gal activity in lysate from cultured skin fibroblasts from these patients. Treatment with NOEV significantly enhanced β-gal activity in cultured skin fibroblasts in the absence of PPCA. CONCLUSIONS: Our results indicate the possibility that NOEV chaperone therapy might have a beneficial effect, at least in part, for patients with galactosialidosis.
Authors: Juan Camilo Losada Díaz; Jacobo Cepeda Del Castillo; Edwin Alexander Rodriguez-López; Carlos J Alméciga-Díaz Journal: Int J Mol Sci Date: 2019-12-29 Impact factor: 5.923